Leber’s hereditary optic neuropathy: Update on the novel genes and therapeutic options

J Chin Med Assoc. 2023 Nov 28. doi: 10.1097/JCMA.0000000000001031. Online ahead of print.


A maternal inheritance disorder called Leber’s hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA disorder. In most studies, there are more male patients than female patients, which contradicts the usual pattern in mitochondrial hereditary diseases. This suggests that nuclear DNA (nDNA) may influence the degeneration of retinal ganglion cells (RGCs) in LHON. The primary cause of this is dysfunction in complex I of the electron transport chain, leading to ineffective ATP production. In addition to MT-ND4 or MT-ND1 mutations, genes such as PRICKLE3, YARS2, and DNAJC30, which come from nuclear DNA, also play a role in LHON. These three genes affect the electron chain transport differently. PRICKLE3 interacts with ATP synthase (complex V) at Xp11.23, while YARS2 is a tyrosyl-tRNA synthetase 2 involved in mitochondria. DNAJC30 mutations result in autosomal recessive LHON (arLHON). Understanding how genes impact the disease is crucial for developing new treatments. Idebenone has been approved for treating LHON and has shown safety and efficacy in clinical trials. Mesenchymal stem cell-based therapy has also emerged as a potential treatment for LHON by transferring mitochondria into target cells. Gene therapy research focuses on specific gene mutations, and the wild-type ND4 gene target in the AAV vector has shown promise in clinical trials as a potential treatment for LHON.

PMID:38016117 | DOI:10.1097/JCMA.0000000000001031